7-76248193-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001110199.3(SRRM3):​c.239C>T​(p.Ser80Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000026 in 1,612,554 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

SRRM3
NM_001110199.3 missense

Scores

1
3
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.48
Variant links:
Genes affected
SRRM3 (HGNC:26729): (serine/arginine repetitive matrix 3) Predicted to enable mRNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.042861372).
BS2
High AC in GnomAd4 at 13 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SRRM3NM_001110199.3 linkc.239C>T p.Ser80Leu missense_variant Exon 3 of 15 ENST00000611745.2 NP_001103669.1 A0A087WXA3
SRRM3NM_001291831.2 linkc.239C>T p.Ser80Leu missense_variant Exon 3 of 16 NP_001278760.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SRRM3ENST00000611745.2 linkc.239C>T p.Ser80Leu missense_variant Exon 3 of 15 5 NM_001110199.3 ENSP00000480851.1 A0A087WXA3
SRRM3ENST00000479294.2 linkn.324C>T non_coding_transcript_exon_variant Exon 2 of 3 2

Frequencies

GnomAD3 genomes
AF:
0.0000854
AC:
13
AN:
152158
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000314
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000366
AC:
9
AN:
245848
Hom.:
0
AF XY:
0.0000224
AC XY:
3
AN XY:
133784
show subpopulations
Gnomad AFR exome
AF:
0.000528
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000559
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000199
AC:
29
AN:
1460278
Hom.:
0
Cov.:
30
AF XY:
0.0000220
AC XY:
16
AN XY:
726264
show subpopulations
Gnomad4 AFR exome
AF:
0.000777
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.0000332
GnomAD4 genome
AF:
0.0000854
AC:
13
AN:
152276
Hom.:
0
Cov.:
32
AF XY:
0.0000940
AC XY:
7
AN XY:
74452
show subpopulations
Gnomad4 AFR
AF:
0.000313
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000658
Hom.:
0
Bravo
AF:
0.000121
ESP6500AA
AF:
0.000638
AC:
2
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000581
AC:
7

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jun 21, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.239C>T (p.S80L) alteration is located in exon 3 (coding exon 2) of the SRRM3 gene. This alteration results from a C to T substitution at nucleotide position 239, causing the serine (S) at amino acid position 80 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.43
CADD
Uncertain
24
DANN
Pathogenic
1.0
Eigen
Benign
-0.11
Eigen_PC
Benign
-0.010
FATHMM_MKL
Benign
0.58
D
LIST_S2
Uncertain
0.89
D
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.043
T
MetaSVM
Benign
-0.66
T
PrimateAI
Uncertain
0.52
T
Sift4G
Uncertain
0.0070
D
Vest4
0.29
MVP
0.043
ClinPred
0.094
T
GERP RS
4.2
gMVP
0.55

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs370360717; hg19: chr7-75877511; COSMIC: COSV58386056; API